Rifabutin treatment methods, uses, and compositions

Abstract

The invention provides formulations containing highly concentrated solutions of rifabutin and methods of making such formulations. The invention also provides methods of using such formulations to treat a bacterial infection in a subject.

What is claimed is: 
     
         1 . A rifabutin formulation produced from a rifabutin powder in the presence of an acid, water, and a solvent suitable to promote dissolution of the rifabutin. 
     
     
         2 . The formulation of  claim 1 , wherein the ratio of rifabutin to solvent w/v is about 1:2. 
     
     
         3 . The formulation of  claim 1 , wherein the solvent is selected from the group consisting of: PEG, propylene glycol, NMP, ethanol, DMA, transcutol HP, and dimethyl isosorbide (DMI). 
     
     
         4 . The formulation of  claim 3 , wherein the solvent is DMI or trascutol HP. 
     
     
         5 . The formulation of  claim 1 , wherein the solvent to water ratio v/v is from about 1:1 to about 1:2. 
     
     
         6 . The formulation of  claim 1 , wherein the acid is selected from the group consisting of:
 hydrochloric, methanesulfonic, phosphoric, L-tartaric, D-glucuronic, L-malic, D-gluconic, L-lactic, acetic and L-aspartic.   
     
     
         7 . The formulation of  claim 6 , wherein the acid is acetic acid or D-glucuronic acid. 
     
     
         8 . The formulation of  claim 1 , wherein the rifabutin to acid molar ratio is about 1:1. 
     
     
         9 . The formulation of  claim 1 , wherein the formulation is diluted in order to produce a composition suitable for a desired route of administration. 
     
     
         10 . A method of preparing a formulation of rifabutin, the method comprising:
 preparing a solution comprising a solvent, water and an acid; and   adding said solution to rifabutin powder, thereby causing the rifabutin to dissolve in the solution.   
     
     
         11 . The method of  claim 10 , wherein the solvent is selected from DMI and tanscutol HP. 
     
     
         12 . The method of  claim 10 , wherein the acid is selected from acetic acid and D-glucuronic acid. 
     
     
         13 . A method of preparing a formulation of rifabutin, the method comprising:
 preparing a solution comprising water and an acid; and   adding said solution to a rifabutin solution in a solvent, thereby producing an aqueous rifabutin formulation.   
     
     
         14 . The method of  claim 13 , wherein the solvent is selected from DMI and tanscutol HP. 
     
     
         15 . The method of  claim 13 , wherein the acid is selected from acetic acid or D-glucuronic acid. 
     
     
         16 . A method of treating a bacterial infection in a subject, the method comprising administering a therapeutically effective amount of rifabutin in an injectable formulation or by inhalation.